Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 5:23 PM
Ignite Modification Date:
2025-12-24 @ 5:23 PM
NCT ID:
NCT03067350
Brief Summary:
Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment.
Main Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.
Detailed Description:
Voriconazole (VRC), the gold-standard treatment of invasive aspergillosis is characterized by variables and nonlinear pharmacokinetics, causing many under- or over-dosing. A link exist between trough plasma concentrations (Cmin) of VRC and effectiveness but also its toxicity. Thus the longitudinal therapeutic drug monitoring of VRC is now recommended with a therapeutic range between 1 and 5 mg/L. The pharmacokinetic variability of VRC is in part explained by its metabolism, mainly dependent on cytochrome P 450 (CYP), particularly CYP2C19, 3A4, 3A5; all these CYP exhibiting genetic polymorphisms. The authors, recently shown, and for the first time , in a retrospective study conducted in 29 patients allogeneic hematopoietic stem cell that initial VRC Cmin adjusted the dose was not only influenced by the route of administration but also by a pharmacogenetics score whose determination is to assign each genotype CYP2C19 and CYP3A a score expressed in a arbitrary units.
The combined pharmacogenetic score was strongly correlated with the original Cmin (r= -0.748; p = 0.002) and was the only independent predictor of initial Cmin (after adjusting the dose and the route of administration). In addition, none of the patients having a genetic score \<2 (ie metabolizing capacity of reduced VRC) did not show an initial Cmin below 1 mg/L, while the initial Cmin was below this threshold efficiency in 47% of patients with a genetic score \>2. The aim of this new study is to confirm the impact of the pharmacogenetic score on the initial VRC Cmin over a larger prospective cohort of 60 adult patients with onco-hematological diseases.
Study:
NCT03067350
Study Brief:
Protocol Section:
NCT03067350